The overall goal of the proposed research is to elucidate the origin of pandemic influenza viruses. Antigenic drift in influenza A viruses is being studied with monoclonal antibodies. Variants are being selected by the passage of influenza viruses in monoclonal antibodies and these are being studied by immunological and biochemical methods. The hemagglutinin molecules of the variants are being peptide mapped and amino acid analyses are carried out on variant peptides. The heterogeneity of the RNAs of human or animal influenza A viruses is being examined to determine if heterogeneity is found in all subtypes. The biological parameters of influenza viruses that replicate in the cells lining the intestinal tract of avian species are being established and naturally occurring recombinants are being characterized antigenically and genetically.